The pancreas is an endocrine-exocrine gland tissue derived from the endoderm, and is constituted by endocrine cells, acinar cells and duct cells. The islets of Langerhans, which are endocrine cells, constitute 1% of the entirety of the pancreas, and are mainly classified into four cells. Namely, they are α cells that secrete glucagon, β cells that secrete insulin, δ cells that synthesize and secrete somatostatin, and F cells that synthesize and secrete pancreatic polypeptides. Among these, insulin that is secreted in β cells has an action of decreasing blood glucose as a major physiological function, and is also a sole hormone that shows a hypoglycemic action. Insulin is secreted in pancreatic β cells by sensing the elevation of blood glucose, and is released into the portal veins. The released insulin suppresses glyconeogenesis and glucose output in the liver and promotes glucose uptake in the fat and muscle tissues that are peripheral tissues, thereby acts to retain the blood glucose level of a living body.
Diabetes mellitus is a persistent hyperglycemia state that is caused by lack of insulin, or lack of the action of insulin. Diabetes mellitus is mainly divided into two kinds: insulin dependent diabetes mellitus (IDDM) that is caused by abnormal secretion of pancreatic insulin by an autoimmune disease or the like, and non-insulin dependent diabetes mellitus (NIDDM) that is caused by the decrease of insulin secretion ability due to pancreatic fatigue accompanied with a persistent high insulin state due to lack of the action of insulin (insulin resistance). Persistent hyperglycemia due to diabetes mellitus causes impairment of blood vessels and also causes complications in multiple organs. Typical complications may include diabetic nephropathy, diabetic retinopathy, diabetic neurosis and the like, and decrease in quality of life (QOL), increase in medical expenses, decrease in survival percentage and the like are seen as problems.
For the therapy of diabetes mellitus, an exercise therapy, a dietary therapy and a drug therapy are conducted. Examples of drugs used for drug therapy include drugs for promoting insulin secretion from pancreatic β cells, drugs for improving insulin resistance, drugs for suppressing absorption of sugar, drugs for promoting utilization of sugar, and the like. Among these, insulin secretagogues are expected to improve diabetes mellitus by suppressing hyperglycemia since they can be expected to have an effect of increasing a blood insulin concentration to decrease blood glucose, and sulfonylurea formulations (SU drugs), rapid-acting insulin secretagogues, DPPIV inhibitors (see Non-Patent Document 1), GLP-1 analogues (see Non-Patent Document 2) and the like are actually used in the fields of the therapy of diabetes mellitus. However, although SU drugs that are most frequently used in Japan stimulate pancreatic β cells and thereby promote endogenous insulin secretion (see Non-Patent Document 3), they exhibit hypoglycemia as a side effect in some cases, and thus require attentions in uses in aged persons, persons with decreased renal function and cases of irregular eating. Furthermore, side effects such as body weight gain have also been reported. In addition, primary failure in which no effect is observed from the time of initial administration, or secondary failure in which a clinical effect is diminished during an administration period occurs in some cases (see Non-Patent Document 4), and thus development of an insulin secretagogue that remits these side effects and is less onerous against pancreatic β cells so as to not impair insulin secreting ability is desired.
As compounds having a condensed pyridine or condensed pyrimidine backbone, a compound having an activity of inhibiting Farnesoid X receptor (FXR) (Patent Document 1), compounds that are useful as therapeutic agents for metabolic diseases (Patent Documents 2 and 3), compounds that are useful as protein kinase inhibitors (Patent Documents 4 and 5), and a compound that is useful as a drug-resistant therapeutic agent (Patent Document 6) have been reported.